KR101605522B1 - Compositions for prevention or treatment of Prion disease containing 2-(3-hydroxy-4-(4-(3-methoxyphenoxy)-1H-pyrazol-3-yl)phenoxy)aceto-hydrazide or pharmaceutically acceptable salts thereof as an active ingredient - Google Patents

Abstract

The present invention relates to a process for the preparation of 2- (3-hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) The present invention relates to a pharmaceutical composition for the prevention and treatment of prion diseases which contains 4- (4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) aceto-hydrazide or a pharmaceutically acceptable salt thereof as an active ingredient Specifically, it has been confirmed that the compound inhibits the formation of prion protein in a concentration-dependent manner and has no cytotoxicity, so that it can be effectively used as an active ingredient of a composition for preventing and treating prion diseases.

Description

(3-hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) aceto- hydrazide, or a pharmaceutically acceptable salt thereof, (3-hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) aceto-hydrazide or pharmaceutically acceptable salts thereof as an active ingredient}

The present invention relates to a process for the preparation of 2- (3-hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) The present invention relates to a pharmaceutical composition for the prevention and treatment of prion diseases which contains 4- (4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) aceto-hydrazide or a pharmaceutically acceptable salt thereof as an active ingredient will be.

Proteinaceous infectious particles (PrP ^Sc ), which are structurally modified normal prions (PrP ^C ) and can be propagated only by proteins without involvement of nucleic acids such as DNA or RNA, Which was first presented by Stanley B. Prusiner in 1982. These are the causes of various neurodegenerative diseases, such as mad cow disease, bovine spongiform encephalophathy (BSE), Creutzfeldt-Jakob disease (CJD) .

Approximately 250 years ago, one of the prion diseases, scrapie, was reported to have occurred in sheep and was reported to be infectious until about 1930. By the 1960s, they had long incubation periods by JS Griffith, Prusiner has succeeded in purifying Prp ^sc , a so-called denatured prion, and previously known as protein infections, has been extended to prion infections.

The prion proteins are of interest because they cause diseases in humans. In the 1920s, it was reported that mad cow disease was caused by human consumption of cows infected with mad cow disease and that Creutzfeldt-Jakob disease (CJD) occurred at that time, , But since then, various forms of prion diseases have appeared in humans, and they are recently classified as very important diseases. In addition to the CJD discovered in the 1920s, Kuru, first discovered in Papua New Guinea, has been considered infectious after prion disease has been found to be infected by ingesting the affected human tissue.

In the 1980s, the nucleotide sequence of the prion gene, PRNP, was identified, and familial CJD (fCJD), Gerstmann-Strussler-Scheinker syndrome (GSS) The mutation of prion genes in patients with fatal familial insomnia (FFI) has been identified and the causes of these diseases have been identified. In the 21st century, it is known that prion disease is transmitted through surgical procedures used in patients infected with prion diseases and transplantation of dura mater and cornea isolated from them. Therefore, the occurrence of iatrogenic CJD (iCJD) Sporadic CJD (sporadic CJD, sCJD) has also been reported, which is reported to be transmitted without mutation or parity of prion genes.

Prion disease is a type of degenerative brain disease, and once it develops, symptoms are very similar to dementia and the mortality rate after onset is 100%. Nevertheless, it is very urgent to develop an inhibitor that inhibits prion diseases in the reality that proper preventive or therapeutic methods have not been found and the method of early diagnosis is insufficient.

Prion disease occurs when abnormal protein folding of normal prion protein (Prp ^c ) results in formation of a depression through formation of denatured prion protein (Prp ^sc ). So far, many researchers have conducted various studies on the mechanism of denaturation of normal prion proteins, but to date, they have not been able to identify any apparent cause. Because the cause of the disease is unclear, the development of therapeutic agents for it is also insufficient. Aguzzi, A., and colleagues at the University of Zurich have suggested that the introduction of the antipyrine gene into prion-null mice can prevent prion diseases by producing antibodies against degenerated prions in the body (Science, 2001. 294: 178-182) However, we concluded that it is difficult to use it as a therapeutic agent because it has antibodies from the time the mouse is born. Stanley B. Prusiner and colleagues report that the use of quinacrine in malaria treatments inhibits the conversion of prion proteins into pathogenic forms (PNAS 2001. 98: 9836-9841) In 2003, Cashman N. and colleagues found that antibodies directly acting on a particular amino acid sequence in a prion protein selectively recognize only the altered prion protein (Nature Medicine 2003. 9: 819-820). Williamson RA, a researcher at the Scripps Research Institute in California, has reported a new fact that the antibody itself can kill neurons when injecting antibodies into the brain of healthy mice and pointed out the risk of brain damage during antibody therapy studies (Science. 2004. 303 -1516) to emphasize the urgency of developing a new therapeutic concept. In 2007, Kazuo Kuwata and colleagues at the University of Gifu University noted that the distance between the 159th aspartic acid (Asp) and the 196th glutamic acid (Glu) was longer than the normal prion, (PNAS, 2007. 104: 11921-11926). ≪ / RTI > It has been confirmed that it can be applied as a therapeutic agent for various prion diseases by inhibiting the denaturation of normal prions and inhibiting the formation of granules.

Accordingly, the present inventors have made efforts to develop a novel therapeutic agent for a prion disease that inhibits the formation of prion protein, and found that 2- (3-hydroxy-4- (4- (3-methoxyphenoxy) -lH-pyrazol-3-yl) phenoxy) aceto-hydrazide] The present inventors have accomplished the present invention by confirming that they can be effectively used as an effective ingredient of a composition for preventing and treating prion diseases since they do not have cytotoxicity.

It is an object of the present invention to provide a process for the preparation of 2- (3-hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol- A pharmaceutical composition for the prevention and treatment of prion diseases, which comprises, as an active ingredient, hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) aceto-hydrazide or a pharmaceutically acceptable salt thereof as an active ingredient Or a health functional food.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing and treating prion diseases, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:

[Chemical Formula 1]

.

.

Another object of the present invention is to provide a health functional food for preventing and ameliorating prion diseases, which comprises the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

(3-hydroxy-4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) aceto- hydrazide [2- The present invention relates to a composition for prevention and treatment of prion diseases and a method for the prevention and treatment of prion diseases, which comprises inhibiting the formation of prion protein in concentration-dependent manner and having no cytotoxicity, It can be usefully used as an active ingredient.

Figure 1 shows a hot spot region for stabilizing a prion monomer.
Figure 2 shows a docked simulated binding mode of GN-8 known to bind at the prion monomer stabilization site.
FIG. 3 is a diagram showing the active skeleton represented in the main active site of the prion monomer. FIG.
FIG. 4 is a graph showing inhibitory effect on the formation of prion proteins by the compound treatment of the present invention.
error bar: error for each measurement; And
RLU: Relative luminescence units.
5 shows a cytotoxicity test by the treatment of the compound of the present invention in normal cells;
(A) The cell survival rate according to the treatment of the compound of the present invention using mouse prion-overexpressing neuron (L2-2B1) represents the average value of five repeated experiments, and error bar represents the error range of each experimental value; And
(B) N2a neuron cells treated with the compound of the present invention.

Hereinafter, terms of the present invention will be described.

As used herein, the term "prophylactic " refers to any act that inhibits the onset or delays the onset of the administration of the composition.

In the present invention, "improvement" or "treatment" means any action in which administration of the composition improves or alters the symptoms of the disease.

In the present invention, "administration" means providing a predetermined substance to a patient in any suitable manner, and the administration route of the composition of the present invention may be oral or parenteral ≪ / RTI > The composition may also be administered by any device capable of transferring the active agent to the target cell.

In the present invention, "Pharmacophore" is a three-dimensional array of chemical groups (or features) that a drug (ligand) must have in order to be effective for a target disease or target protein. In particular, the definition of the active framework is very important in order for a compound to bind to a protein and increase or inhibit the activity of the protein. The active framework consists of a feature called a hydrogen bonder (HBA), a hydrogen bond acceptor (HBD), and a hydrophobic lip (Lipo), which are suitably combined and expressed in the form of a map.

Hereinafter, the present invention will be described in detail.

The present invention relates to a process for the preparation of 2- (3-hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) aceto-hydrazide [ Prevention and treatment of prion diseases containing an active ingredient as the active ingredient, or a pharmaceutically acceptable salt thereof, which comprises administering to a patient in need thereof a therapeutically effective amount of at least one compound selected from the group consisting of 3-hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol- There is provided a pharmaceutical composition comprising:

[Chemical Formula 1]

.

.

The compound preferably inhibits prion protein invasion but is not limited thereto.

The prion disease is preferably mad cow disease, bovine spongiform encephalophathy (BSE), or Creutzfeldt-Jakob disease (CJD), but is not limited thereto.

In a specific embodiment of the present invention, the present inventors have searched for a novel drug based on a protein structure to select a compound represented by the above formula (1) expected to be active in the stabilization of a prion monomer, Biological experiments were conducted to verify the inhibitory effect (see Figures 1 to 3).

In addition, the present inventors confirmed that the compounds of the present invention inhibit the formation of prion proteins by inhibiting the formation of prion proteins. As a result, it was confirmed that the compounds selected in the present invention inhibited the formation of prion protein in a concentration-dependent manner (see FIG. 4).

Furthermore, the present inventors confirmed that the compounds of the present invention do not exhibit toxicity to the two neurons of L2-2B1 cells and N2a (see FIG. 5).

Accordingly, the present invention provides a method for producing 2- (3-hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol- hydroxy-4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) aceto-hydrazide] inhibits the formation of prion protein in a concentration-dependent manner, Can be used as a pharmaceutical composition.

The present invention encompasses a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof, and a possible solvate, hydrate, racemate, or stereoisomer thereof, which can be prepared therefrom.

Can be used in the form of a compound represented by the general formula (1) of the present invention or a pharmaceutically acceptable salt thereof, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. Acid addition salts include those derived from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, and aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxyalkanoates, Dioleate, aromatic acid, aliphatic and aromatic sulfonic acids. Such pharmaceutically innocuous salts include, but are not limited to, sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate chloride, bromide, Butyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, succinate, maleic anhydride, maleic anhydride, , Sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, Methoxybenzoate, phthalate, terephthalate, benzene sulfonate, toluene sulfonate, chlorobenzene sulfide Sulfonate, methanesulfonate, propanesulfonate, naphthalene-1-sulphonate, naphthalene-1-sulphonate, , Naphthalene-2-sulfonate or mandelate.

The acid addition salt according to the present invention can be obtained by a conventional method, for example, by dissolving the compound represented by the formula (1) in an excess amount of an acid aqueous solution, and mixing the salt with a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile ≪ / RTI >

It is also possible to prepare the same by heating the compound represented by the general formula (1) and an acid aqueous solution or alcohol, followed by evaporating the mixture or drying the precipitated salt by suction filtration.

In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is preferable for the metal salt to produce sodium, potassium or calcium salt. The corresponding silver salt is also obtained by reacting an alkali metal or alkaline earth metal salt with a suitable salt (such as silver nitrate).

When the composition is formulated, it is prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used.

Solid formulations for oral administration include tablets, patients, powders, granules, capsules, troches and the like, which may contain one or more excipients such as starch , Calcium carbonate, sucrose or lactose, or gelatin. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions or syrups. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like are included in addition to commonly used simple diluents such as water and liquid paraffin. .

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like.

Examples of the non-aqueous solvent and suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerol, gelatin and the like can be used.

The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the type of disease, severity, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents, and can be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.

Specifically, the effective amount of the compound according to the present invention may vary depending on the age, sex, and body weight of the patient. In general, 0.1 mg to 100 mg, preferably 0.5 mg to 10 mg per kg of body weight is administered daily or every other day Or one to three times a day. However, the dosage may be varied depending on the route of administration, the severity of obesity, sex, weight, age, etc. Therefore, the dosage is not limited to the scope of the present invention by any means.

The present invention also relates to a process for the preparation of 2- (3-hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) Prevention of prion diseases containing an active ingredient of [2- (3-hydroxy-4- (4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) aceto- hydrazide] or a pharmaceutically acceptable salt thereof And health functional foods for improvement:

[Chemical Formula 1]

.

.

The compound preferably inhibits prion protein invasion but is not limited thereto.

The prion disease is preferably mad cow disease, bovine spongiform encephalophathy (BSE), or Creutzfeldt-Jakob disease (CJD), but is not limited thereto.

(3-hydroxy-4- (3-methoxyphenoxy) -1H-pyrazol-3-yl) phenoxy) aceto- hydrazide [2- Hydrazide] inhibits the formation of prion protein in a concentration-dependent manner, and has no cytotoxicity. Therefore, it can be used for the prevention and improvement of prion diseases And can be usefully used as an active ingredient of foods.

Hereinafter, the present invention will be described in detail with reference to Examples, Experimental Examples and Production Examples.

However, the following Examples, Experimental Examples and Preparation Examples are merely illustrative of the contents of the present invention, and the scope of the present invention is not limited by Examples, Experimental Examples and Preparation Examples.

< Example  1> Excavation of substances through search of virtual new drug based on protein structure

Precipitation by prions occurs as a result of a change in the structure of a normal prion monomer, resulting in the death of neurons in aggregates of denatured prions. And to develop a substance that inhibits the induction of mad cow disease by inhibiting the conversion to metamorphic prion and aggregation through normal prion monomer stabilization.

Specifically, a literature review was conducted on a substance that inhibits the accumulation of denatured prions by binding with a primary binding site (hot spot region) that induces stabilization of a normal prion monomer. The major amino acids that interact with compounds at known known binding sites are asparagine (Asn) 159, glutamine (Gln) 160, lysine 194, and aspartate 196 (Fig. In order to generate an active framework suitable for the main binding site, the binding mode was first docked simulated through a representative known substance (GN-8) known to bind to the main active site (FIG. 2).

The coupling mode extracted by the docking simulation was compared with the coupling mode of the data which determined the coupling mode through the quantitative calculation through the literature investigation to determine suitability. Analysis of binding mode by docking simulation revealed interaction with key amino acids at major binding sites. The backbone carbonyl (C = O, carbonyl) group of glutamine 160 serves as a hydrogen bond acceptor, and the nitrogen of the backbonamide group acts as a hydrogen bond leader to form a hydrogen bond with GN-8. It was confirmed that the hydrogen in the side chain of lysine 194 had two hydrogen bonding interactions due to the role of hydrogen bond and simultaneously observed hydrophobic interaction with the alkyl group of the side chain of lysine 194 .

Based on the above interaction with GN-8 and key amino acids of major binding sites, active skeleton was generated. Finally, the selected active framework consists of the following elements. Hydrogen bond to the backbone carbonyl group of asparagine 159, hydrogen bond to the oxygen of the amide group of glutamine 160 side chain, hydrogen bond to the nitrogen of the side chain of lysine 194, In the space across the two hydrophobic elements.

In order to express not only the interaction factors but also the binding pattern of the major binding site of the prion monomer, 5 to 6 amino acids were selected from the core amino acids and set to an exclusive volume (FIG. 3).

The library for virtual drug discovery is organized in the form of Discovery Studio / CatDB by Accelrys. The compounds are designed to detect multiple conformation of a three-dimensional structure and to define all possible chemically possible conformers. parameters were well controlled. A compound library containing about 7 million species was constructed. All compounds included in the virtual search compound library constructed using Discovery Studio's 'Search 3D Database' protocol were searched. The various forms of isomers of each compound were mapped to the active skeleton, and fitness was measured by evaluating whether the interaction elements set in the active skeleton and the atom or the substructure of the compound molecule were appropriately located. We select a highly conformable form isomer in one molecule and evaluate whether the selected form isomer has significant fit. Through the above process, compounds having the same characteristics as those of active skeleton were finally selected out of 400 million compounds. Through a virtual search, 1,110 compounds were selected as virtual leader materials. The basic goal of virtual search is to select compounds that have primarily structural diversity through the active framework. Therefore, among the 1,110 compounds, structurally similar groups were classified using FCFP (Functional Circular Fingerprint) method, which is one of the molecular fingerprinters, in order to select compounds considering structural diversity.

Prior to selecting the final inducted material, a focused database was generated that is expected to be active in stabilizing the prion monomer. A key database of substances expected to be active in prion monomers will be an important infrastructure for future detection of degenerated prion inhibitors. A total of 300 compounds were synthesized and the final 31 compounds were selected by measuring the similarity between the molecules in 300 compounds. Of the 20 commercially available compounds, a compound described by the following formula (1) was selected and a biological experiment was conducted to verify the effect of inhibiting denatured prion formation.

[Chemical Formula 1]

.

.

< Example  2> Prion  Protein Formation of boulders  Verification of inhibitory effect

The normal prion protein consists of 42% of α-helix and 3% of β-sheet structure, but denatured prion protein forms a secondary structure with β-sheet structure increasing to 43% . The Multimer Detection System (MDS), which was developed using these characteristics, is an experiment for measuring only multimeric prion proteins. When the compound selected in Example 1 was treated with prion protein, And the effect of the inhibitor was verified by measuring the degree of inhibition.

Specifically, the compounds selected in Example 1 were solubilized at a concentration of 50 mM using DMSO and stored at -20 DEG C until use. The compound was treated with three concentrations of 0.5 μM, 10 μM and 100 μM immediately before use, and the mixture was mixed with 80 ng of recombinant human prion protein (ajROBOSCREEN), and reacted in a 37 ° C. incubator with stirring for 3 hours. Then, two types of anti-prion antibodies (3E7-ajROBOSCREEN, T2-HRP - Japan NIAH Laboratories) required for capturing and detecting were reacted in the incubator for 1 hour in an incubator at 37 ° C, and light was emitted using an ECL substrate The luminescence value was measured using a luminometer to evaluate the degree of inhibition of multimer formation. In addition, the positive control (rHuPrP) used recombinant human prion protein and the negative control was Tris buffered saline-Tween 20 (TBS-T).

As a result, as shown in FIG. 4, in the group treated with the compound selected in Example 1, 62%, 79%, and 92% of multimers were produced in comparison with the positive control group (Fig. 4).

< Example  3> Cytotoxicity check

In order to evaluate the toxicity of the compound selected in Example 1 to cells, MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, invitrogen) was applied. In the case of normal cells, MTT was reduced by reductase in mitochondria to form formazan crystals, and the degree of killing by the toxicity of the compound was evaluated by measuring the crystals thus formed by a spectroscopic method .

Specifically, N2a neuron (ATCC) And mouse prion-overexpressing cells (L2-2B1) (obtained from the common infections acquired by the National Institute of Health). Each cell was spread on a 96-well plate at ⁴ × 10 ⁴ / well, The selected compounds were cultured in a CO ₂ incubator at 37 ° C for 24 hours at concentrations of 0.5 μM, 10 μM, 30 μM, 60 μM and 100 μM. At this time, the negative control group treated PBS with the same dose instead of the inhibitor. Then, 100 μl of MTT dissolved in PBS at a concentration of 5 mg / ml was added to each well, followed by incubation at 37 ° C. in a CO ₂ incubator for 4 hours. After 4 hours of incubation, the MTT solution was removed and 100 μl of DMSO was added. The reaction was carried out for 30 minutes. The absorbance was measured at 550 nm using a spectrophotometer. The OD values of the inhibitors were compared with those of the negative control.

As a result, as shown in FIG. 5, it was confirmed that the compounds of the present invention did not show toxicity to both L2-2B1 cells and N2a neurons (FIG. 5).

< Manufacturing example  1> Manufacture of Pharmaceuticals

One. Sanje  Produce

500 ng of the compound of the present invention

Lactose 1 g

The above components were mixed and packed in airtight bags to prepare powders.

2. Preparation of tablets

500 ng of the compound of the present invention

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

3. Preparation of capsules

500 ng of the compound of the present invention

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.

4. Preparation of injections

500 ng of the compound of the present invention

180 mg mannitol

Na2HPO42H2O 26 mg

Distilled water 2974 mg

According to the conventional method for preparing an injectable preparation, an injectable preparation was prepared by incorporating the aforementioned components in the amounts indicated.

Claims (6)

1. A pharmaceutical composition for the prevention and treatment of prion diseases, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Chemical Formula 1]

.
The pharmaceutical composition for preventing and treating prion diseases according to claim 1, wherein the compound inhibits prion protein invasion.
The method according to claim 1, wherein the prion disease is mad cow disease, bovine spongiform encephalophathy (BSE), or Creutzfeldt-Jakob disease (CJD) A pharmaceutical composition.
A health functional food for preventing and improving a prion disease comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Chemical Formula 1]

.
The health functional food for preventing and improving prion diseases according to claim 4, wherein said compound inhibits prion protein invasion.
The method according to claim 4, wherein the prion disease is mad cow disease, bovine spongiform encephalophathy (BSE), or Creutzfeldt-Jakob disease (CJD). Health functional foods.

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